Method and installation for setting in adsorbed state on a porous support active compounds contained in a product

ABSTRACT

The invention concerns a method and an installation for setting in adsorbed state, on a porous support, compounds contained in a product comprising a first step which consists in extracting the compounds by contacting the product with at least a solvent at supercritical pressure to obtain a mixture of extracts and solvent. The method is characterized in that it comprises a second step which consists in eliminating the water contained in the mixture of extracts and solvent, adjusting the temperature and pressure conditions so as to obtain, a first phase consisting of solvent in gaseous state and a second phase consisting of a mixture of liquids formed of solvent and extracts of the products; causing said two phases to trickle through a porous support adapted to adsorb the extracts; vaporizing the solvent contained in the second phase.

This application is a 371 of PCT/FR00/02668, filed Sep. 27, 2000, basedon foreign application FRANCE 9912005, filed Sep. 27, 1999.

BACKGROUND OF THE INVENTION

The present invention relates to a method and an installation allowing,industrially, the setting in adsorbed state, on a porous support, ofcertain active compounds contained in natural or synthetic products.More precisely, such an operation will be effected after a preliminaryphase during which said active compounds will be extracted from theseproducts with the aid of a solvent taken to supercritical pressure, i.e.a fluid in supercritical state or a subcritical liquid.

In effect, it is known that bodies are generally known in three states,namely solid, liquid or gaseous, and that one passes from one to theother by varying the temperature and/or the pressure. Now, there is apoint beyond which one can pass from the liquid state to the gaseous orvapour state without passing via a boiling or, inversely, acondensation, but continuously: this point is called the critical point.

It is also known that a fluid in supercritical state, i.e. a fluid whichis in a state characterized either by a pressure and a temperaturerespectively greater than the critical pressure and temperature in thecase of a pure body, or by a representative point (pressure,temperature) located beyond the envelope of the critical points shown ina diagram (pressure, temperature) in the case of a comparison with thatobserved in this same fluid in the state of compressed gas. The sameapplies to the so-called “subcritical” liquids, i.e. liquids which arein a state characterized either by a pressure higher than the criticalpressure and by a temperature lower than the critical temperature in thecase of a pure body, or by a pressure higher than the critical pressuresand a temperature lower than the critical temperatures of the componentsin the case of a mixture (cf. on this subject the article by MichelPERRUT—Les Techniques de l'Ingénieur “Extraction by supercritical fluid,J 2 770-1 to Dec. 1999”).

The considerable and modulatable variations of the solvent power of thesupercritical fluids are, moreover, used in numerous methods ofextraction (solid/fluid), fractionation (liquid/fluid), analytical orpreparative chromatography, treatment of materials (ceramics, polymers .. . ). Chemical or biochemical reactions are also made in such solvents.It should be noted that the physico-chemical properties of carbondioxide as well as its critical parameters (critical pressure: 7.4 MPaand critical temperature: 31° C.) make of it the preferred solvent innumerous applications, all the more so as it does not present anytoxicity and is available at very low price in very large quantities.Non-polar solvent, the carbon dioxide taken to supercritical pressuresometimes has a co-solvent added thereto, constituted in particular by apolar organic solvent whose function is to considerably modify thesolvent power, especially with respect to molecules presenting a certainpolarity, ethanol often being used to that purpose. However, certaincompounds are more favourably extracted with a light hydrocarbon havingfrom 2 to 5 carbon atoms, and more favourably, from 2 to 4 carbon atoms,at supercritical pressure.

One of the principal advantages of the methods using fluids atsupercritical pressure as solvents resides in the facility of effectingthe separation between the solvent and the extracts and solutes, as hasbeen described in numerous publications and, for certain importantaspects of implementation, in French Patent FR-A-2 584 618. Theinteresting properties of these fluids have, moreover, been used for along time in solid-fluid extraction and liquid-fluid fractionation, ashas been described in the article mentioned above.

In the event of the extracts or solutes comprising very volatileproducts, such as odorant products, the mere separation by partialdecompression bringing about separation of the solutes and theircollection by phase separation with the fluid, is not very efficient andthe fluid, even partially decompressed, still contains substantialquantities of such substances. In order to separate these substancesfrom the fluid before its recycling, it is known to use an adsorbent bedwhich will fix these substances and purify the fluid, as described forexample in Japanese Patent JP-A-02139003.

Finally, it is known that the extraction of natural products by a fluidat supercritical pressure leads to extracts of very high quality whichare increasingly used in numerous applications. However, such extracts,lie, moreover, the extracts obtained with other means such as forexample extraction by organic solvent, are often in the form of veryviscous or even pasty products which are not easy to handle, with theresult that their incorporation in solid supports, the dosage and themixture with a matrix and possibly other active principles, within asolid excipient, are very difficult. One is sometimes obliged to placethem in solution in an organic solvent in order to effect impregnationof a solid excipient, which is regrettable since there thus disappears adetermining advantage in numerous applications for which any contact ofthe product with an organic solvent is to be avoided.

SUMMARY OF THE INVENTION

The present invention has for its object to propose means making itpossible, for purposes of industrial production, to extract activeprinciples, particularly of pharmaceutical, cosmetological, dieteticinterest, from diverse raw materials in which they are diluted, invariable concentration, depending on the origin of these raw materialsand the period of their harvesting, as is always the case for productsof natural origin, and to fix the extract obtained in the course ofextraction in an adequate porous matrix by impregnation in one and thesame operation.

According to the invention, the operation of extraction by fluid atsupercritical pressure is coupled with a second operation during whichthe separation of the extract mixed with the solvent fluid and theimpregnation of a porous medium by this extract are effectedsimultaneously.

The present invention thus has for its object a method for setting inadsorbed state, on a porous support, compounds contained in a product,in which, during a first step, the extraction of the compounds iseffected by contacting the product with at least one solvent fluid atsupercritical pressure leading to the obtaining of a mixture of extractsand of solvent fluid, characterized in that, in a second step, the watercontained in the mixture of extracts and of solvent fluid is eliminated,the temperature and pressure conditions are adjusted so as to obtain, inan enclosure, two phases, namely a first phase essentially constitutedby the solvent fluid in the gaseous state and a second phase constitutedby a mixture of liquids formed by solvent fluid and extracts of theproduct, these two phases are made to trickle through a porous supportadapted to adsorb the extracts, the solvent fluid contained in thesecond phase is vaporized.

The elimination of the water will preferably be ensured by causing themixture of extracts and of solvent fluid to trickle over a bed ofadsorbent product adapted to fix the water selectively.

The solvent fluid may be constituted by pure carbon dioxide, nitrogenprotoxide or a light hydrocarbon counting from 2 to 4 carbon atoms. Thesolvent fluid may be pure or possibly have one of more co-solvents addedthereto. For example, the solvent fluid may in particular be constitutedby a mixture of carbon dioxide with at least one co-solvent constitutedby an alcohol and preferably ethanol, by a ketone and preferablyacetone, by an ester and preferably ethyl acetate.

The first step of extraction may preferably be effected at a pressureincluded between 7.4 MPa and 80 Mpa, and preferably between 10 MPa and40 MPa, and at a temperature included between 0° C. and 80° C.Similarly, the trickling of the two phases through the porous supportmay be effected at a pressure included between 1 MPa and 10 MPa, andpreferably between 4 MPa and 8 Mpa, and at a temperature includedbetween 0° C. and 80° C.

The present invention also has for its object an installation forextraction/impregnation of the type comprising an extractor containing aproduct from which it is desired to extract the compounds, which istraversed to that end by at least one solvent fluid at supercriticalpressure, characterized in that it successively comprises, downstream ofthe extractor, means for eliminating the water contained in theextracted compounds, means adapted to create, in an impregnationenclosure containing a porous medium, two phases, namely a first phaseessentially constituted by the solvent fluid in the gaseous state and asecond phase constituted by a mixture of liquids formed by solvent fluidand the extracts of the product, so as to effect the adsorption by theporous medium of the extracted compounds. The impregnation enclosure maycomprise means for contributing enthalpy, particularly constituted by adouble envelope with circulation of heat-exchange fluid.

The installation may also comprise, downstream of the impregnationenclosure, means for condensation of the solvent fluid.

In a variant embodiment of the invention, the extractor may beconstituted by a fractionating column operating in counter-flow, adaptedfor the treatment of liquid raw materials.

Various forms of embodiment of the present invention will be describedhereinafter by way of non-limiting examples, with reference to theaccompanying single Figure which schematically shows an installation forcarrying out the method according to the invention.

As has been described in detail in the article and the Patent mentionedhereinabove, it is known that the methods of extraction and offractionation using a fluid at supercritical pressure comprise twosuccessive steps: a first step during which the solvent fluid iscontacted with the raw material to be treated, under such pressure andtemperature conditions that its solvent power with respect to thecompounds to be extracted is high, and a second step during which thefluid is placed under such pressure and temperature conditions that itssolvent power is very weak with respect to the products which it hasextracted from the raw material during the earlier step, which allowsthe separation of these extracts, the fluid then being recycled. Unlikethe conventional embodiments consisting in separating the two phasesobtained during this second step in gravity or inertia separators, themethod according to the invention consists in causing the mixture ofthese two phases to trickle within a porous medium.

It has been noticed that, if the operation is carried out withoutparticular precaution, the extracts are not distributed homogeneously onand within the porous medium and, even by proceeding with stirring ofthis porous medium if it is in pulverulent or granular form, for examplewith the aid of a rotating turbine, lumps of variable size are generallyobtained, resulting from the agglomeration of the particles of theporous medium by the extracts which, instead of penetrating in thepores, remain on the surface without homogeneous distribution. Moreover,natural products, capable of being advantageously treated by a method ofthis type, always having a certain content of water, the extracts alwayscontain water of which the presence complicates their adsorption on theporous supports or excipients, as the majority of them have a greataffinity for water, so that their structure and their mechanicalproperties are seriously altered by the water thus contributed by thefluid at the same time as the extracts envisaged.

On the contrary, when the water is trapped, particularly by a selectiveadsorbent, and the impregnation of the porous medium is then effectedunder determined pressure and temperature conditions, it is observedthat, surprizingly, the extracts impregnate this porous medium in veryhomogeneous and reproducible manner, leading for example to a non-stickypowder presenting a good fluidity in the case of the initial porousmedium also presenting these characteristics.

BRIEF DESCRIPTION OF THE INVENTION

An example of installation for carrying out the method according to theinvention will be described hereinafter with reference to the singleFIGURE showing components of a system for extraction.

DETAILED DESCRIPTION OF THE INVENTION

This installation is derived from a conventional unit of extraction byfluid at supercritical pressure intended for the discontinuous treatmentof solid materials. It comprises an extractor 1 containing a basket 2intended to receive the raw material to be treated, and a diaphragm pump3 which distributes liquid carbon dioxide at the working pressure,through a heat exchanger 4 making it possible to heat the fluid to theworking temperature. Unlike the conventional installations forextraction by fluid at supercritical pressure, the fluid emerging fromthe extractor 1 is conducted in a recipient 5 which contains a porousmedium for selectively adsorbing water, such as in particular themolecular sieve 3A. The fluid which is under the same pressure andtemperature conditions as those prevailing in the extractor 1, tricklesthrough the porous medium where it abandons the water that it contains.

The recipient 5 is connected to a pressure reducing valve 8 via aheater-exchanger 7. The outlet of the valve 8 is connected to the bottomof an impregnation enclosure 9 which contains the porous medium 10 inwhich it is desired to adsorb the extracts. The enclosure 9 comprisesheating means constituted for example by a double envelope 11 in which aheat exchange fluid circulates. The fluid leaving the recipient 5 isthus taken to a state of desired pressure and temperature determinedduring its passage in the exchanger 7 and the pressure reducing valve 8,so that it comprises a gaseous phase and a liquid phase. The heatingmeans constituted by the double envelope 11 make it possible to vaporizeliquid phase arriving in the impregnation enclosure 9, so as to maintainconstant the level of liquid phase therein. Under these conditions, agaseous phase is therefore had permanently in the impregnation enclosure9, constituted by solvent fluid and a liquid phase constituted by theextracts and the solvent fluid.

The porous medium 10 is chosen as a function of the subsequent use whichit is desired to make of the final product, whether it be a granular orpulverulent medium particularly adapted for use in dietetics, pharmacyor cosmetics, or a solid medium. In the most frequent case where thismedium is in granular or pulverulent form, a particularly advantageousembodiment consists in string this porous medium within the impregnationenclosure 9 by any adequate means, for example by means of a turbine 14moved by an electric motor 16 via a magnetic drive system 18.

The upper part of the enclosure 9 is joined to the pump 3 through acondenser 12.

Of course, it is possible, according to the invention, to use any otherseparation system, and the extractor 1 might be replaced by afractionating column making possible the continuous or discontinuoustreatment of raw materials in the liquid state, the fluid emerging fromthe column being treated in the same manner as that describedpreviously.

In a variant of the invention, an auxiliary pump is used for introducingin the extractor 1 one or more organic co-solvents making it possible tomodify the solvent power and the polarity of the solvent fluid. It isoften chosen to add ethanol which may be of alimentary quality or CODEXdepending on the destination of the products thus elaborated. A lighthydrocarbon having between 2 and 8 carbon atoms may also favourably beused as co-solvent. In the case of a co-solvent being used, a porousmedium which is not altered by this co-solvent will naturally be chosen.Moreover, at the end of the extraction-impregnation operation, care willbe taken to scavenge the porous medium with pure solvent fluid withoutco-solvent in order to eliminate the adsorbed co-solvent.

It has been ascertained that, under these conditions, an excellentdiffusion of the fluid was obtained through the pores of the porousmedium, and, correlatively, the entrainment in these latter of theextracts and their adsorption in the pores.

A contribution of enthalpy is required to maintain a constant quantityof fluid in the liquid state within the impregnation enclosure 9, inproportion as the fluid coming from extraction is injected and as anidentical delivery of fluid which emerges from this enclosure in thegaseous state is therefore vaporized. This contribution of enthalpy mustbe carefully adjusted in order to avoid, if it is insufficient, eitherthe accumulation of liquefied fluid in the impregnation recipient whichwould finish by emerging in this liquid form, taking along part of theextracts, or, if it is too great, the total vaporization of the fluidand the non-controlled precipitation of the extracts.

As will be illustrated in the following examples of implementation ofthe method and of the installation according to the invention, it issurprizing to effect extraction and to obtain a very homogeneousimpregnation of different excipients by the extracts in one operation,without ever having to manipulate the extracts themselves, which can butavoid all risk of degradation by oxidation in air or by exposure toheat, since any contact with air is avoided and all the operations areconducted at a temperature close to ambient temperature.

Several examples of the invention which were carried out with theinstallation described hereinabove and whose operational parameters wereas follows, will be described hereinafter:

Volume of the basket 2 0.5 l Flowrate of the pump 3 1 to 5 kg/hr Workingpressure of the order of 30 MPa Working temperature between 10° C. and80° C. Contents of recipient 5 100 g of zeolite 3A Volume ofimpregnation 4.5 l enclosure 9 Porous material Maltodextrine powder ofalimentary quality obtained by partial hydrolysis of maize amide Speedof rotation of 120 revs/minute the turbine 18

EXAMPLE 1 Extraction and Impregnation of KAVA-KAVA

Kava-kava is the local name of a wild shrub of the Pacific islands,identified as Piper methysticum or Piper wichmannu, whose roots containproducts of great pharmacological interest called kavalactones, widelyused in different forms as natural tranquillizer and euphoriant.

The extraction was conducted on 100 g of powder of dried roots, groundtowards about 200 μm, with a flowrate of 3 kg/hr of carbon dioxide at 25MPa and 40° C., and furnished an extract which is in the form of a veryviscous, dark yellow paste with characteristic odour. After adsorptionof the water, the pressure of the fluid was reduced to 6 MPa andinjected via the bottom into the impregnation enclosure 9 containing 100g of maltodextrine. It was observed that the compressed gas leaving thetop of the enclosure 9 presented a constant temperature close to 40° C.in established operation. After having continued the operation for 510mins., the impregnation enclosure 9 was decompressed and 114.8 g of abright yellow powder was recovered therein, which presented thecharacteristic odour of the extract of kava-kava and flowing withoutproblem in the absence of any lump or agglomerate, ideal formanufacturing tablets, possibly mixed with an excipient or other activeprinciples. A sample of this powder was re-extracted with chloroform andanalyzed by gas-chromatography. It was ascertained that the extractfixed on the maltodextrine was constituted by 89% by mass ofkavalactones whose identification makes it possible to verify that therelative abundance of each of these compounds is conforming to what isfound in a conventional extract. This therefore confirms both the highselectivity of the extraction by the carbon dioxide at supercriticalpressure and the complete fixation of the extract on the maltodextrine.

EXAMPLE 2 Extraction and Impregnation of KAVA-KAVA

A second operation was proceeded with under conditions identical tothose used in Example 1, except that, this time, the initial mass ofmaltodextrine was only 50 g. After 510 mins. of operation, 65.6 g ofpowder were obtained, whose characteristics are identical to those ofthe powder obtained in Example 1, except that its colour and odour aremore intense. An analysis of the fixed extract revealed a percentage ofkavalactones of 91% by mass, with a distribution between the differentcompounds virtually identical to that observed in the preceding Example.This shows that the maltodextrine may be charged with at least 30% bymass of extract.

EXAMPLE 3 Extraction and Impregnation of KAVA-KAVA

A third operation was proceeded with under conditions identical to thoseused in Example 2, except that, this time, a porous medium was chosen,composed of an intimate mixture of powders of maltodextrine and sojalecithin of alimentary quality, at a rate of 45 g of maltodextrine for 5g of lecithin. The initial mass of porous medium was fixed at 50 g.After 510 mins. of operation, 64.2 g of powder were obtained, whosecharacteristics proved to be close to those of the powder obtained inExample 1, except that its colour and odour are more intense. Ananalysis of the fixed extract led to a percentage of kavalactones of 90%by mass, with a distribution between the different compounds virtuallyidentical to that observed in the preceding Example. This powder thuspresents the advantage, with respect to the powders obtained in Examples1 and 2, of being more easily dispersed in water, giving rise to aturbidity resembling that obtained by diluting pastis in water. It maytherefore be used not only in dry formulations, such as tablets, butalso in the form of a powder to be mixed in water in order to prepare adrinkable potion.

EXAMPLE 4 Extraction and Impregnation of a Spice (Curcuma)

The extraction was conducted on a total mass of 800 g of ground Curcuma,distributed in 4 batches of 200 g placed successively in the extractor 1with a flowrate of 2.4 kg/hr of carbon dioxide at 40° C. and 29 MPa.After elimination of the water, the pressure of the latter was reducedto 5 MPa and it was injected via the bottom in the impregnationenclosure 9 containing a mass of 400 g of maltodextrine which wassuccessivly impregnated with the extracts issuing from the four batches.After having continued the operation for four periods of 50 mins. each,445 g of a very homogeneous orange powder were recovered, presenting theodour and characteristic taste of the extract of Curcuma.

EXAMPLE 5 Extraction and Impregnation of a Mixture of Spices (BlackPepper+Mild Paprika)

One proceeded with an operation of extraction and impregnation of thespices under conditions identical to those used in Example 4, exceptthat, this time, the charge was constituted by a mixture of 180 g ofpepper and 20 g of paprika. After having passed 8.4 kg of carbondioxide, 412 g of very homogeneous red powder were obtained, in theabsence of lump or agglomerate.

What is claimed is:
 1. Method for setting in absorbed state, within on aporous support, compounds contained in a starting material, comprisinga. contacting, at supercritical pressure, the starting material with asolvent fluid comprising at least one solvent to obtain a mixture ofextracts and solvent fluid; b. contacting the mixture of extracts and ofsolvent fluid with a bed of absorbent product adapted to absorb waterselectively; c. adjusting the temperature and pressure conditions of themixture of extracts and solvent fluid exiting from the absorbent bed toobtain a first phase consisting essentially of the solvent fluid in thegaseous state and a second phase comprising a mixture of solvent fluidand extracts from the starting material; d. contacting the first andsecond phases with a porous support adapted to absorb the extracts; e.vaporizing the solvent fluid contained in the second phase.
 2. Methodaccording to claim 1, wherein the solvent fluid is constituted by carbondioxide, by nitrogen protoxide or by a light hydrocarbon having from 2to 8 carbon atoms.
 3. Method according to claim 2, wherein the solventfluid has at least one co-solvent added thereto.
 4. Method according toclaim 3, wherein the solvent fluid co-solvent is constituted by analcohol, and/or by a ketone, and/or by an ester.
 5. Method according toclaim 1, wherein the solvent fluid is a pure fluid.
 6. Method accordingto claim 1, wherein the solvent fluid has at least one co-solvent addedthereto.
 7. Method according to claim 6, wherein the co-solvent isconstituted by an alcohol, and/or by a ketone, and/or by an ester. 8.Method according to one of claims 1-7, wherein step (a) is effected at apressure included between 7.4 MPa and 80 MPa, and at a temperatureincluded between 0° C. and 80° C.
 9. Method according to claim 8,wherein step (d) is effected at a pressure included between 1 MPa and 10MPa, and at a temperature included between 0° C. and 80° C.
 10. Methodaccording to claim 8, wherein step (a) is effected at a pressureincluded between 10 MPa and 40 MPa.
 11. Method according to claim 10,wherein step (d) is effected at a pressure included between 1 MPa and 10MPa, and at a temperature included between 0° C. and 80° C.
 12. Methodaccording to one of claims 1-7, wherein step (d) is effected at apressure included between 1 MPa and 10 MPa, and at a temperatureincluded between 0° C. and 80° C.
 13. Method according to claim 12,wherein step (a) is effected at a pressure included between 4 MPa and 8MPa.
 14. Installation for extraction/impregnation of the typecomprising, in serial connection: an extractor adapted to accept astarting material for extraction and to allow at least one solvent fluidat supercritical pressure pass over the starting material producing amixture of solvent fluid and extracted compounds; an vessel comprising amaterial selected to absorb water from the mixture of solvent fluid andextracted compounds; an impregnation enclosure comprising a porousmedium selected to absorb extracts, the enclosure associated with meansfor contributing enthalpy, the means adapted to create, in theimpregnation enclosure, a first phase consisting essentially of thesolvent fluid in the gaseous state and a second phase comprising amixture of liquids formed by solvent fluid and the extracts of theproduct, the porous medium and enthalpy effective to effect absorptionby the porous medium of extracted compounds.
 15. Installation accordingto claim 14, wherein the means for contributing enthalpy is a doubleenvelope jacket for circulating heat-exchange fluid.
 16. Installationaccording to claim 14, comprising a pressure reducing valve between thevessel and the impregnation enclosure.
 17. Installation according to oneof claims 14-16, wherein the extractor is a fractionating columnoperating in counter-flow, adapted for the treatment of liquid rawmaterials.
 18. Installation according to claim 17, comprising aninjector of injecting an organic co-solvent within the solvent fluid.19. Installation according to one of claims 14-16, comprising aninjector for injecting an organic co-solvent within the solvent fluid.